194 research outputs found

    Effects of hTERT on genomic instability caused by either metals or radiation or combined exposure

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    There is currently a great interest in delayed chromosomal damage and other damaging effects of low-dose exposure to a variety of agents, which appear collectively to act through induction of stress-response pathways related to oxidative stress (and aging). These agents have been studied mostly in the radiation field but evidence is accumulating that chemicals, especially heavy metals, can also act in the same manner. Therefore, this work investigated the effects of metals and/or radiation in human fibroblasts in vitro. Humans are exposed to metals, including chromium (CR) VI) and vanadium (V) (V) from the environment, industry and surgical implants. Thus the impact of low-dose stress responses may be greater than expected from individual toxicity projections. In this study, a short (24 hours) exposure of human fibroblasts to low doses of Cr (VI) and V (V) caused both acute chromosome damage and genomic instability in the progeny of exposed cells for a t least 30 days after exposure. Acutely, Cr (VI) caused chromatid/ breaks without aneuploidy while V (V) caused aneuploidy without chromatid breaks. The long-term genomic instability was similar but depended on hTERT positivity. In telomerase-negative hTERT- cells, CR (VI) and V (V) caused a long lasting and transmissible induction of dicentric chromosome, nucleoplasmic bridges, micronuclei and aneuploidy. There was also a long term and transmissible reduction of clonogenic survival, with and increased b-galactosidase staining and apoptosis. This instability was not present in telomerase positive hTERT + cells. In contrast, in HTERT + cells the metals caused a persistent induction of tetraploidy, which was not noted in hTERT-cells. Interestingly, the clonogenic assay demonstrated that radiation induced genomic instability in hTERT + cells and to a lesser extent, in hTERT-cells. This showed that the telomerase activity in hTERT+cells did not provide protection against genomic instability caused by the radiation insult. Furthermore, neither 0.05 Gy nor 0.5 Gy doses of radiation induced chromosomal instability in either types of cells used (hTERT-and hTERT + cells). However, hTERT + cells had a slight higher incidence of micronuclei, immediately after radiation exposure of 0.5 Gy compared to hTERT- cells. Similarly to the metal only experiments, there was a higher level of tetraploidy in the hTERT+cells compared to the hTERT-cells, although it only reached a level of statistical significance immediately after the radiation exposure of the 0.05 Gy dose. This finding was different to what was seen for the metal only treated [CR (VI)] cells, where hTERT-cells showed significant cell damage and this damage was less compared to hTERT+cells. Combined exposure caused loss of clonogenic survival and therefore genomic instability in both types of cells (hTERT – and hTERT + cells). This genomic instability was more pronounced in hTERT + cells after Metal Followed by Radiation, and it was more pronounced in hTERT- cells after Radiation Followed by Metal. Similarly, cytogenetic damage was higher in hTERT+ cells after Metal Followed by Radiation, and higher in hTERT- cells after Radiation Followed by Metal. Similar to the metal only experiments, there was a higher level of tetraploidy in the hTERT +cells compared to the hTERT-cells, although it did not reach a level of statistical significance. It appears that the biological effects provoked by combined exposure of metal and radiation has led to a synergistic action in both types of cells, compared to metal treatment only or radiation exposure only. In fact, in most of the significant results, the damage caused by the combination of metal and radiation was higher than the damage induced by either metal itself or radiation itself. Similarly to the radiation only experiments, it was interesting to observe that ectopic hTERT expression had no effect in preventing the lost of clonogenic survival, as well as the formation of cell damage after combined exposure. This was in contrast to metal only treated [CR (VI)] cells, where hTERT – cells showed cell damage which was less compared to that observed in hTERT+cells. This study suggests that the type of genomic instability caused by metals in human cells may depend critically on whether they are telomerase-positive or – negative. However, the type of genomic instability caused by either radiation or combined exposure to metals and radiation in human cells appears to be not prevented by telomerase activity

    Appellate Review in Bifurcated Trials

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    Reliability and Utility of a Lumbopelvic-hip Complex Stability Assessment in Individuals with Patellofemoral Pain

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    OBJECTIVE Lumbopelvic-hip complex (LPHC) stability is related to altered movement patterns that are present in individuals with PFP. Current studies measuring LPHC function in PFP primarily assess endurance and not stability. A test of isolated LPHC stability, the Seated Trunk Control Test (STCT) was recently developed and test-retest reliability for the STCT has been shown to be excellent in a healthy population. To improve the clinical usefulness of the STCT, we aimed to establish test-retest reliability for individuals with PFP. We hypothesized the STCT would show good-to-excellent reliability. We also compared STCT performance between healthy individuals and those with PFP. We hypothesized those with PFP would have lower TTE and greater NE. MAIN OUTCOME MEASURESPerformance was measured as time to first error (TTE) and number of errors (NE) averaged between test trials. Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) assessed test-retest reliability utilizing a two-way mixed-effects model with single rater (ICC[3,1]). The Mann-Whitney U Test compared performance measures between groups, p \u3c 0.05

    Effect of Fatigue on Lumbopelvic-Hip Complex Muscle Activation and Lower Extremity Biomechanics

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    Please enjoy Volume 6, Issue 1 of the JSMAHS. In this issue, you will find Professional, Graduate, and Undergraduate research abstracts, and case reports. Thank you for viewing this 6th Annual OATA Special Edition

    Bioactive Compounds from Marine Sponges and Algae: Effects on Cancer Cell Metabolome and Chemical Structures

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    Metabolomics represent the set of small organic molecules generally called metabolites, which are located within cells, tissues or organisms. This new “omic” technology, together with other similar technologies (genomics, transcriptomics and proteomics) is becoming a widely used tool in cancer research, aiming at the understanding of global biology systems in their physiologic or altered conditions. Cancer is among the most alarming human diseases and it causes a considerable number of deaths each year. Cancer research is one of the most important fields in life sciences. In fact, several scientific advances have been made in recent years, aiming to illuminate the metabolism of cancer cells, which is different from that of healthy cells, as suggested by Otto Warburg in the 1950s. Studies on sponges and algae revealed that these organisms are the main sources of the marine bioactive compounds involved in drug discovery for cancer treatment and prevention. In this review, we analyzed these two promising groups of marine organisms to focus on new metabolomics approaches for the study of metabolic changes in cancer cell lines treated with chemical extracts from sponges and algae, and for the classification of the chemical structures of bioactive compounds that may potentially prove useful for specific biotechnological applications

    Integrating multiple genome annotation databases improves the interpretation of microarray gene expression data

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    <p>Abstract</p> <p>Background</p> <p>The Affymetrix GeneChip is a widely used gene expression profiling platform. Since the chips were originally designed, the genome databases and gene definitions have been considerably updated. Thus, more accurate interpretation of microarray data requires parallel updating of the specificity of GeneChip probes. We propose a new probe remapping protocol, using the zebrafish GeneChips as an example, by removing nonspecific probes, and grouping the probes into transcript level probe sets using an integrated zebrafish genome annotation. This genome annotation is based on combining transcript information from multiple databases. This new remapping protocol, especially the new genome annotation, is shown here to be an important factor in improving the interpretation of gene expression microarray data.</p> <p>Results</p> <p>Transcript data from the RefSeq, GenBank and Ensembl databases were downloaded from the UCSC genome browser, and integrated to generate a combined zebrafish genome annotation. Affymetrix probes were filtered and remapped according to the new annotation. The influence of transcript collection and gene definition methods was tested using two microarray data sets. Compared to remapping using a single database, this new remapping protocol results in up to 20% more probes being retained in the remapping, leading to approximately 1,000 more genes being detected. The differentially expressed gene lists are consequently increased by up to 30%. We are also able to detect up to three times more alternative splicing events. A small number of the bioinformatics predictions were confirmed using real-time PCR validation.</p> <p>Conclusions</p> <p>By combining gene definitions from multiple databases, it is possible to greatly increase the numbers of genes and splice variants that can be detected in microarray gene expression experiments.</p

    Roe enhancement of Paracentrotus lividus: Nutritional effects of fresh and formulated diets

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    Sea urchin gonads are exploited both for gastronomic and scientific purposes; thus, the production of large and mature gonads is essential. Natural populations of the Mediterranean Sea urchin Paracentrotus lividus are subject to increasing fishing ef- forts, due to continuous intensification of consumptions. Aquaculture practices may represent an answer, but the availability of artificial feeds accelerating the produc- tion of high-quality gonads in terms of size, taste, colour, firmness, maturity and via- bility of gametes is critical to boost the productions. The accessibility of cheap and effective feeds promoting the fattening of gonads and the quality of gametes is still a bottleneck slowing down the expansion of echinoculture practices. This investiga- tion is aimed at enabling the development of this strategic sector, by comparing the dietetic effects of fresh foods and a commercial feed for aquaculture, to four newly formulated feeds. The protein contents of diets were strongly related to the GSIs. The abundance of fatty acids appeared inversely related to the viability of embryos and abnormalities of larvae. The features of an ideal diet for this sea urchin were defined, based on the results of experimental trials, and the need for increasing levels of plant-derived proteins during the grow-out period was demonstrated
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